, 1984 and Pickles et al., 1989). Mechano-electrical transduction (MET) adaptation presents as a decrease in current during a constant stimulus, where further stimulation recovers Olaparib in vitro the current
(Crawford et al., 1989 and Eatock et al., 1987). Adaptation is implicated in setting the hair bundle’s dynamic range, providing mechanical tuning, setting the hair cell’s resting potential, providing amplification to an incoming mechanical signal, and providing protection from overstimulation (Eatock et al., 1987, Farris et al., 2006, Fettiplace and Ricci, 2003, Hudspeth, 2008, Johnson et al., 2011, Ricci and Fettiplace, 1997 and Ricci et al., 2005). Fundamental hypotheses regarding hair cell adaptation originated from work in low-frequency hair cells contained in the frog saccule, turtle auditory papilla, and mammalian utricle (Assad et al., 1989, Corey and Hudspeth, 1983a, Crawford et al., 1989, Crawford et al., 1991, Eatock et al., 1987, Hacohen et al., 1989 and Howard and Hudspeth, 1987). Two components of adaptation, termed fast and slow (motor),
are distinct in their operating range, kinetics, and underlying mechanisms (Wu et al., 1999); however, Ca2+ entry via the MET channel drives both processes. To generate fast adaptation, Ca2+ is postulated to interact directly with the channel or through an accessory protein (Cheung and Corey, 2006, Choe et al., 1998, Crawford et al., 1989, Crawford et al., 1991 and Gillespie Phosphatidylinositol diacylglycerol-lyase and Müller, 2009); however,
Akt inhibitor myosin motors Ic, VIIa, and XVa have also been implicated in regulating fast adaptation (Kros et al., 2002, Stauffer et al., 2005 and Stepanyan and Frolenkov, 2009). A long-standing slow adaptation model posits that movement of myosin isozymes up and down the stereocilia controls the tension sensed by the MET channels in a Ca2+-dependent manner (Assad and Corey, 1992, Assad et al., 1989, Holt et al., 2002 and Howard and Hudspeth, 1987). Recent data questions whether motor adaptation is relevant to mammalian auditory hair cells. Myosin Ic, the presumptive adaptation motor, does not specifically localize to the upper tip link insertion site in mammalian auditory hair cells, and its expression during development does not match the onset of slow adaptation (Schneider et al., 2006 and Waguespack et al., 2007). Furthermore, the kinetics of myosin Ic do not fit the requirements of the model in terms of climbing and slipping rates (Pyrpassopoulos et al., 2012). Additionally, MET channels are localized to the tops of stereocilia (Beurg et al., 2009) and not at the upper insertion site where myosin motors are thought to reside; therefore, it is unlikely that Ca2+entering through MET channels is directly responsible for regulating these motors.